An established approach to the understanding of the physiological operations of the brain is to examine neuronal responses to controlled sensory stimuli and motor responses at successive levels of brain hierarchy. Whereas this approach will continue to generate a wealth of information about sensory processes and motor control alternative strategies for revealing the cognitive operations of the neuronal networks are warranted. Sensory inputs can be precisely defined and systematically varied. However, cognitive processes are inferred from introspection and/or indirectly from behavior, making it difficult to interpret the relationship between behavior and neuronal activity in highly associational areas, such as the hippocampus. Here, we operationally define cognitive operation as coordinated neuronal activity (a) that is added to the incoming information and/or (b) which generates behavior beyond the control of sensory inputs. The main assumption of our proposed research is that variability of spike times in the hippocampus, not accounted for by the physical features of sensory inputs, is due to brain-derived processes. Accordingly, we will test the hypothesis that spike train variability in neuronal populations (i. e., in functional cell assemblies) shows coordination beyond that predicted by the time-course of sensory input. To address these issues, we will use large-scale parallel recording of unit activity in both hippocampus and neocortical structures of behaving rats. Coordinated functional assemblies will be searched for within the hippocampus and between hippocampus and neocortex. Perturbation of spike outputs and synaptic weights, by electrical stimulation of small groups of cells and individual neurons, will be used to change assembly membership of neurons. In essence, our program offers an alternative approach for identifying brain-generated processes without direct reference to a priori cognitive terms. The dysfunction of these hypothesized, cooperative mechanisms may contribute to human diseases, such as Alzheimer's, schizophrenia and epilepsy.